A General Mathematical Model of Symport Based on Conformational Transitions

Abstract

General mathematical modeling of symport faces two fundamental challenges: (i) a unified kinetic description independent of protein-specific structural details; and (ii) quantitative cross-scale mapping between microscopic conformational transitions and macroscopic physiological observables. Grounded in the fundamental physiological principle of cellular homeostasis, we propose a unifying hypothesis for symporter gating: symporters actively regulate intracellular concentrations of specific solutes within thermodynamically feasible bounds. Based on this hypothesis, we construct a universal mathematical model of symporters, employing a minimal conformational cycle as the topological scaffold and probabilistic transition rates to quantitatively describe conformational interconversion kinetics. Model simulations of experimental data from the SGLT, NaPi-II, NKCC, and NBC transporter families yield consistent fits. The resulting parameters not only reproduce experimentally observed transport behaviors---but also reveal underlying mechanistic principles of symporter function.